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New studies explain how cancer cells 'eat us alive'

September 1, 2010

Four key studies now propose a new theory about how cancer cells grow and

survive, allowing researchers to design better diagnostics and therapies to

target high-risk cancer patients. These studies were conducted by a large team

of researchers at Jefferson University's Kimmel Cancer Center.

This new idea also explains why so many cancer patients say that " their cancer

is eating them alive " - an accurate observation that has never been understood,

the researchers say.

These four new studies, co-published in the September issue of the journal Cell

Cycle, provide evidence that tumor growth and metastasis is directly " fueled " by

normal supporting cells.

These supporting cells are called fibroblasts, and they produce the stroma

(connective tissue) that surrounds tumor cells. As the cancer progresses,

increasing numbers of these stromal cells eat themselves to provide recycled

nutrients to tumor cells - leading to dramatic weight loss in patients.

They also found that without recycled nutrients provided by fibroblasts, tumor

cells are more fragile and die. Based on this breakthrough, the researchers

propose that available drugs (now on the market), which sever the " parasitic "

connection between tumor cells and fibroblasts, may be effective therapeutics.

" We think we have finally figured out how cancer really works - and this

reverses 85 years of dogma, upon which current cancer research and therapy is

based, " says the study's senior investigator, P. nti, M.D., Ph.D.,

Chairman of Jefferson's Department of Stem Cell Biology & Regenerative Medicine.

The prevailing theory, known as the Warburg Effect, developed by German

researcher Otto Warburg in 1924 (for which he won a Nobel prize), says that

tumor cells change their metabolism in order to fuel their own growth. As

evidence, Warburg pointed to a lack of mitochondria, which are tiny " power

plants, " in laboratory cancer cells, saying these cells have found another way

to produce the energy they need.

Pestell, MB, BS, MD, Ph.D, FRACP, director of the Kimmel Cancer Center

and co-author on these studies notes, " These studies suggest that the absence of

mitochondria in laboratory cancer cells may reflect in part that cultured cells

have had to adjust to life outside of their original environment, without their

stromal partner. " Drs. nti, Pestell and colleagues found this out by

performing a simple experiment in which they mixed cancer cells and fibroblasts

together, and then searched for mitochondria. The found the fibroblasts didn't

have any mitochondria, and that the cancer cells had all the mitochondria.

" The Warburg Effect is happening, but it is happening to fibroblasts, not to

cancer cells. Fibroblasts have no mitochondria because they are eating them to

provide energy to cancer cells, and cancer cells have a ton of mitochondria

because they need these power plants to process all the recycled nutrients given

to them by fibroblasts, which then helps them grow and spread, " Dr. nti

says.

They have dubbed this finding " The Reverse Warburg Effect. "

" It's amazing, " Dr. nti says. " Much of what we know about cancer is

backwards because cancer researchers used isolated tumor cells for most cancer

studies. Now, when we put cancer cells back in their stromal environment, we see

how cancer cells critically depend on fibroblasts for their survival. "

Tumor cells do this by employing oxidative stress as a weapon. Then, oxidative

stress in fibroblasts " tricks " these stromal cells into eating themselves to

feed cancer cells, the researchers say. This process of " self-eating " or

" self-cannibalism " is called autophagy.

During periods of starvation, normal cells undergo autophagy. This metabolic

re-programming allows cells to recycle nutrients by continually eating

themselves, including their mitochondria. This permits starving cells to recycle

nutrients and to survive under hostile conditions.

Now, Dr. nti and colleagues have figured out how cancer cells take advantage

of this recycling process. To satisfy their large appetite, hungry cancer cells

induce oxidative stress in the fibroblasts and this stress forces the stromal

cells to eat themselves, which provides recycled nutrients or " food " to fuel

survival of nearby cancer cells.

" It's that simple. Cancer cells are eating us alive by stealing nutrients from

normal cells using oxidative stress, and by employing those recycled nutrients

to support their own growth. Stem cells are then recruited from the bone marrow

to produce fresh fibroblasts, to continually fuel cancer cell growth, " Dr.

nti says. " For years, cancer patients have said they felt as though the

cancer in their body was eating them alive. These patients were right.

Essentially, the cancer knows how to induce oxidative stress and turns a local

wasting process into a whole-body phenomenon. "

To read the full article, click on this link:

http://www.physorg.com/news202553643.html